The overall objectives of the proposed research are to investigate the effects of renin activity and hypertension on atherogenesis. The specific aims of the proposed study are: (1) to determine if the rate of atherogenesis is related to renin levels; (2) to separate the relative effects of serum cholesterol levels, blood pressures, and plasma renin levels on atherogenesis; (3) to analyze the lipid composition of the lesions produced by the different stimuli studied; and (4) to determine if vasculature pathology can be correlated with the various atherogenic stimuli. The high cholesterol rabbit has been chosen as the primary model. Superimposed upon this model will be various types of hypertension, e.g., one-kidney and two-kidney hypertension. These two models will also provide a basis for the differential stimulation of renin activity. A DOCA-saline model will be included as a normotensive low-renin model. The biochemical parameters to be measured include: (1) plasma renin activity; (2) plasma aldosterone levels; (3) plasma cholesterol levels; and (4) plasma electrolytes. Indirect blood pressure determinations will also be performed throughout the study period. At the termination of the various experimental regimens the rabbits will be sacrificed for necropsy. Vasculature tissue will be examined grossly, histologically, histochemically, and biochemically. Comprehensive lipid analysis, including lipoprotein assays will be performed. Specifically, purified total lipid extracts will be prepared from intima-media tissue lesions as well as from plasma. From these preparations, phospholipids and neutral lipids will be separated and quantitated by column chromatography and gravimetric analysis. The component subclasses, such as phosphatidylethanolamines and sphingolipids will be isolated and quantitated by TLC and gravimetric determinations. The fatty acyl composition of each major subclass will be determined by GLC. Plasma lipoproteins will be isolated and purified by ultra-centrifugation and agarose electrophoresis. Delipidated proteins will be studied using disc-gel electrophoresis.